There is an epidemic of cardiovascular disease (CVD) among American Indians. The Strong Heart Study (SHS) has been examining CVD and its risk factors by conducting a longitudinal cohort study and a family genetic study among 13 communities in 3 geographic areas (Arizona, the Dakotas, and Oklahoma). This application proposes to extend the SHS to pursue the following aims: 1) Expand the genetic studies that will emphasize the genome scan approach, but also include investigation of carefully selected candidate genes. The completed genome scan of 3776 members from 94 extended families will be used to identify quantitative trait loci and narrow the regions of interest by fine mapping. We also will examine a selected number of candidate genes that are difficult to exclude on the basis of linkage studies, but are of potential importance to vascular disease. 2) Continue the mortality and morbidity surveillance of the original cohort (approximately2859 male and female survivors, ages 60-89 years) and to initiate annual mortality surveillance and limited morbidity follow-up of the non-cohort family members. 3) Re-examine the family members so that changes in risk factors can be analyzed and genetic effects on changes estimated. Advantages of the SHS include: 1) It provides health data on an underserved ethnic group, 2) It is the largest, longest longitudinal study in the US of CVD and its risk factors in individuals with diabetes, 3) Data from cardiac, carotid, and popliteal ultrasound measures will substantially improve understanding of mechanisms of vascular disease in diabetes and the genetics of CVD, 4) This population includes a group in which the epidemic of obesity and diabetes has impacted people at very young ages, permitting analysis of genetic and environmental effects on these conditions with limited confounding by age effects. SHS will lead to valuable therapeutic and prevention strategies for this and other populations in the US and the world, where the epidemics of obesity, diabetes and CVD are progressing rapidly. The relevance of this research to public health: The SHS studies diseases of the heart and blood vessels in American Indian Communities, in order to try to explain the rapid increases that have been recently observed. The study is attempting to learn about predictors of disease, and to see to what extend it runs in families. SHS is valuable because it provides information on how diabetes leads to diseases of the heart and blood vessels that will be useful in many populations who now have high rates of diabetes. (End of Abstract)